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Immunobiology. 2015 Jul;220(7):859-64. doi: 10.1016/j.imbio.2015.01.005. Epub 2015 Jan 22.

Toll-like receptor 9 dependent interferon-α release is impaired in severe asthma but is not associated with exacerbation frequency.

Author information

1
Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, UK. Electronic address: Aw287@le.ac.uk.
2
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
3
Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, UK.
4
Department of Respiratory Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Oxford, UK.
5
Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, UK; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.

Abstract

Patients with asthma and chronic obstructive pulmonary disease (COPD) are susceptible to exacerbations, often caused by microbial pathogens. We hypothesised that intracellular Toll-like receptor (TLR) function in blood mononuclear cells (PBMCs) from these subjects would be impaired and that this impairment is related to exacerbation frequency. PBMCs stimulated with a TLR-9 agonist (but not TLR-3 or 7/8) produced significantly less IFN-α in asthma (26 [3-696]pg/ml) compared to control (943 [164-1651]) and COPD (597 [127-1186]) subjects (p = 0.0019) but this was not related to the number of exacerbations per year in asthma or COPD. In COPD, IFN-α levels were related to KCO (% predicted) in COPD (r = -0.41, p = 0.01). IFN-α was derived from plasmacytoid dendritic cells (pDCs) and their frequency was lower in asthma compared to control subjects (control 0.48% [0.33-0.64] versus asthma 0.29% [0.13-0.34], p = 0.019) whereas pDC function per se was not significantly impaired between groups. The mechanism underlying reduced IFN-α production and the clinical consequences in severe asthma remains to be established.

KEYWORDS:

Asthma; COPD; Emphysema; IFN-α; pDC

PMID:
25662572
DOI:
10.1016/j.imbio.2015.01.005
[Indexed for MEDLINE]

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